PROJECT SUMMARY/ABSTRACT Compared to the general population, people with SMI smoke more cigarettes per day, are less likely to quit, and have higher levels of nicotine dependence. Lifetime smoking rates of 50-85% are associated with elevated rates of chronic disease and dramatic early mortality among people with SMI, with life expectancy 25-30 years less than in the general population. Most smokers with SMI want to be smoke-free, but their biological vulnerability to nicotine addiction makes cessation rare and relapse to smoking common. Cessation programs target smokers who are actively trying to quit, leaving highly addicted smokers who have tried and failed or are not ready to quit with no options to minimize their risk of harm from continued smoking. The main addictive component in tobacco, nicotine, is not toxic in cigarette doses, and is available in a novel product, electronic cigarettes (e-cigarettes). Early research suggests that e-cigarette vapor does not contain the toxins and carcinogens found in tobacco smoke. E-cigarettes may be particularly appealing as a nicotine delivery system because they address the behavioral (hand-to-mouth) component of smoking. Moreover, e-cigarettes are widely available and popular; almost ? of cigarette smokers in the general population have tried them. Two studies suggest that smokers with SMI have tried this product at similar rates. Based on these studies, we conducted a preliminary pilot study of 19 chronic smokers with SMI who were provided with a 4-week supply of e-cigarettes. Participants significantly reduced their use of cigarettes (by nearly 66%) from baseline to the final study visit, confirmed by a significant decrease (by almost 50%) in mean breath carbon monoxide level, and e-cigarette use did not escalate, suggesting addiction did not worsen. Besides this pilot study, little data exists that fully characterizes the appeal and impact of e-cigarettes in chronic smokers with SMI. The goals of this proposed study are to evaluate the behavioral and psychological appeal of e-cigarettes (Aim 1); to evaluate the toxicity of e-cigarettes compared to tobacco smoke (Aim 2); and to explore the impact of e-cigarettes on nicotine addiction (Exploratory Aim). We will accomplish these aims by randomly assigning 240 chronic smokers with SMI to either receive e-cigarettes for 8 weeks with assessments or to receive assessments only. Theoretically, elimination of carbon monoxide and tar would greatly reduce toxicity compared to combusted tobacco; therefore, this study may have implications for improving health outcomes for other smokers who struggle to quit and are at high risk from continued smoking, such as smokers with cancer.